Disconnected and Hyperactive: A Replication of Sensorimotor Cortex Abnormalities in Patients With Schizophrenia During Proactive Response Inhibition.

Abstract

Inhibitory failure represents a core dysfunction in patients with schizophrenia (SP), which has predominantly been tested in the literature using reactive (ie, altering behavior after a stimulus) rather than proactive (ie, purposefully changing behavior before a stimulus) response inhibition tasks. The current study replicates/extends our previous findings of SP exhibiting sensorimotor cortex (SMC) hyperactivity and connectivity abnormalities in independent samples of patients and controls. Specifically, 49 clinically well-characterized SP and 54 matched healthy controls (HC) performed a proactive response inhibition task while undergoing functional magnetic resonance imaging and resting-state data collection. Results indicated that the majority of SP (84%) and HC (88%) successfully inhibited all overt motor responses following a cue, eliminating behavioral confounds frequently present in this population. Observations of left SMC hyperactivity during proactive response inhibition, reduced cortical connectivity with left SMC, and increased connectivity between left SMC and ventrolateral thalamus were replicated for SP relative to HC in the current study. Similarly, negative symptoms (eg, motor retardation) were again associated with SMC functional and connectivity abnormalities. In contrast, findings of a negative blood oxygenation level-dependent response in the SMC of HC did not replicate. Collectively, current and previous findings suggest that SMC connectivity abnormalities may be more robust relative to evoked hemodynamic signals during proactive response inhibition. In addition, there is strong support that these SMC abnormalities are a key component of SP pathology, along with dysfunction within other sensory cortices, and may be associated with certain clinical deficits such as negative symptoms.